The present invention refers to a novel, simple and inexpensive process for manufacture of an oxetane, which process provides technical as well as environmental advantages. The process includes subjecting an alcohol, having at least two hydroxyl groups, to a reaction with a carbamide compound in the presence of at least one catalyst.
Oxetanes as disclosed and produced by the process of the present invention are compounds having at least one four-membered ring of general formula (I) 
Oxetanes have been prepared by a number of synthetic methods. The generally available methods include
ring closure of 1,3-diol derivatives by the intramolecular Williamson reaction,
decomposition of cyclic carbonate esters, and
photochemical reaction of aldehydes and ketones with olefines.
The intramolecular Williamson reaction consists in general of the reaction of 1,3-halohydrins or their acetates with alkali. In 1878 trimethylene oxide, oxetane, was prepared for the first time by treating 3-chloropropanol with potassium hydroxide. 1,3-halohydrins and acetates thereof have since been widely used in the preparation of oxetanes. The use of acetate esters of said halohydrins often improves the oxetane yield. Hydrogen sulphate esters and sulphate esters are reported as replacements for 1,3-halohydrins in the intramolecular Williamson reaction. Mono(arenesulphonate) esters of 1,3-diols have also been used, especially for preparation of bicyclic oxetanes. Spiro-oxetanes have been prepared by treating di(phenylsulphates) with alkali.
Cyclic carbonate esters of diols decompose to oxetanes and carbon dioxide. The decomposition is normally carried at 160-260xc2x0 C. in the presence of a basic catalyst.
Photochemical reaction of aldehydes and ketones with olefines (the so called Paterno-Bxc3xcichi reaction) comprises generally that an olefine and an aldehyde or ketone are irradiated in an inert atmosphere by a high-pressure mercury lamp.
Further methods for preparation of oxetanes are disclosed in the patent literature, including
British patent no. 787,406 disclosing a process for preparing oxetanes, which process comprises reacting a triol with a carbonic acid derivative of formula Oxe2x95x90C(X)2 wherein X is a halogen atom or an alkyloxy, cycloalkyloxy, aryloxy or tetrahydrofurfuryloxy radical. Compounds included in said formula are for instance phosgene, monoesters of chlorocarbonic acid and diesters of carbonic acid. The conversion proceeds in two stages and the reaction in respective step is dependent on employed carbonic acid derivative. The use of toxic and highly hazardous compounds such as phosgene renders the process a large number of disadvantages and drawbacks.
Japanese Unexamined Patent Publication HEI 10-7669 teaches a method for manufacturing an oxetane having a hydroxymethyl group. The method comprises causing a triol to react with an alkyl or alkylene carbonate yielding a cyclocarbonate compound which subsequently is decarboxylated in the presence of an alkaline catalyst The applicability of disclosed process is substantially limited by the fact that employed carbonates are too expensive for normal industrial use.
Oxetanes can, furthermore, be derived from other oxetanes by for instance electrolysis, oxidation over a silver catalyst, cyclisation by the Freund reaction or by substitution of halogen atoms.
Commonly used methods for preparation of oxetanes, the properties of prepared oxetanes as well as their polymerisation are thoroughly discussed in handbooks and encyclopaedias such as xe2x80x9cEncyclopedia of Polymer Science and Technologyxe2x80x9d, chapter xe2x80x9cOxetane Polymersxe2x80x9d, vol 9, 1968, pp 668-701, John Wiley and Sons Inc.
The present invention provides unexpectedly a novel, simple, inexpensive and reliable process for production of an oxetane, which process provides technical as well as environmental advantages. The process can be summarised by below simplified reaction scheme (I) 
wherein R1 is xe2x80x94NH2 or xe2x80x94NRxe2x80x2Rxe2x80x3, wherein Rxe2x80x2 and Rxe2x80x3 is for instance hydrogen or alkyl, and wherein R2 and R3 may be a group such as alkyl, aryl or hydroxyalkyl. The process comprises subjecting an alcohol having two or more hydroxyl groups, which alcohol most preferably has at least one 1,3diol grouping, to a reaction with a carbamide at a molar ratio employing 1-2 moles of said carbamide on 1-2 moles of said alcohol, in the presence of at least one catalyst promoting and/or initiating transcarbonylation and/or pyrolysis. Preferred embodiments of the process of the present invention employ 1-1.2 mole of said carbamide on 1-1.8 mole of said alcohol. The reaction yields a reaction mixture comprising said oxetane, which subsequently is recovered by means of for instance distillation and/or extraction. The reaction is suitably performed in an inert atmosphere, such as nitrogen and/or argon atmosphere, and/or at a pressure of 0.01-1 bar, such as 0.1-0.5 bar. The reaction temperature is in preferred embodiments 100-250xc2x0 C., such as 110-150xc2x0 C. and/or 170-240xc2x0 C. A suitable amount of catalyst is normally found within the range of 0.01-10 mole%, such as 0.5-2 mole%, calculated on moles of said alcohol, said carbamide and said catalyst. The reaction can also optionally be carried out in the presence of one or more solvents, such as an ethylene glycol, a propylene glycol, a butylene glycol, a hexanol, a heptanol, an octanol and/or a dodecanol. Suitable amount of said solvent is for instance 0.05-2, such as 0.1-1 or 0.2-0.5, moles on 1 mole of carbamide and alcohol.
A typical procedure can be exemplified as follows:
Carbamide and alcohol are mixed in for instance a molar ratio of 2:1 to 1:2, such as a 1:1 to 1:1.8, and at least one catalyst is added in the range of 0.01 to 10 mole %, such as 0.5 to 2 mole %, based on total moles of reactants and catalyst. Optionally, combinations of two or more catalysts can be used. The pressure in the reaction vessel is reduced to 0.01-1 bar, such as 0.1-0.5 bar. Optionally, a stream of an inert gas, such as nitrogen or argon, is passed through the vessel. The inert gas may be used combined with or instead of the reduced pressure. The temperature is then raised to 110-150xc2x0 C., whereby a transcarbonylation starts. The temperature is preferably kept at 120-140xc2x0 C. for 1 to 12 hours, such as 2 to 5 hours, or until the transcarbonylation is completed. A pyrolysis occurs subsequent to said transcarbonylation. The pressure is preferably reduced to 0.05 to 0.15 bar, such as 0.07 to 0.1 bar, and the temperature is slowly raised to 170 to 240xc2x0 C., such as 180 and 200xc2x0 C. The oxetane formed is suitably for instance continuously distilled off from yielded reaction mixture.
The preferred carbamide employed in the process of the present invention is as disclosed previously a compound of general formula (II) 
wherein both substituents R1 are xe2x80x94NH2 or wherein each substituent R1 independently is xe2x80x94NRxe2x80x2Rxe2x80x3, wherein Rxe2x80x2 is hydrogen, linear or branched alkyl having for instance 1-12, such as 1-8, carbon atoms or is part of a bond between the nitrogen atoms in the two substituents Rxe2x80x2 thus being part of a ring formation, and wherein Rxe2x80x3 is hydrogen or linear or branched alkyl having for instance 1-12, such as 1-8, carbon atoms. Carbamide is thus understood as for instance urea, N-alkylurea and N,N-dialkylurea. The preferred carbamide is urea, whereby the two substituents R1 are xe2x80x94NH2.
The alcohol reacted with said carbamide according to the process of the present invention is in preferred embodiments a compound of general formula (III) 
wherein each R2 and R3 independently is alky, alkyloxy, alkyloxyalkyl, aryloxyalkyl, hydroxyalkyl, hydroxyalkyloxy, aryl or hydroxyaryl and wherein each R4 independently is hydrogen or alkyl. Said alkyl is preferably linear or branched alkanyl or alkenyl having 1 to 24 such as 3-24, 1-12, 4-12 or 2-8, carbon atoms.
The alcohol is in the most preferred embodiments of the present invention selected from the group consisting of 2,2-dialkyl-1,3-propanediols, 2-alkyl-2-hydroxyalkyl-1,3-propanediols and 2,2-di(hydroxyalkyl)-1,3-propanediols and/or from the group consisting of dimers, trimers and polymers of said 1,3-propanediols. These alcohols can suitably be exemplified by neopentyl glycol, 2-methyl-2-propyl-1,3-propanediol, 2-ethyl-2-butyl-1,3-propanediol, trimethylolethane monoallyl ether, trimethylolpropane monoallyl ether, pentaerythritol diallyl ether, pentaerythritol monoallyl ether, trimethylolethane, trimethylolpropane, ditrimethylolethane, ditrimethylolpropane, pentaerythritol, dipentacrythritol, tripentaerythritol and esters of dimethylolpropionic acid. Further preferred embodiments include selectively alkoxylated 1,3-propanediols such as 2-alkyl-2-hydroxyalkoxy-1,3-propanediols, 2,2-di(hydroxyalkyloxy)--1,3-propanediols, wherein alkyloxy is linear or branched having for instance 3-24, such as 4-12 carbon atoms, or selectively alkoxylated dimers, trimers or polymers thereof Said selectively alkoxylated 1,3-propanediols can be exemplified by selectively ethoxylated and/or propoxylated trimethylolethane, trimethylolpropane, pentaerythritol, ditrimethylolethane, ditrimethylolpropane, dipentaerythritol or tripentaerythritol. A selectively alkoxylated 1,3-propanediol or dimer, trimer or polymer thereof as disclosed above is understood as a derivative wherein the hydroxyl groups of the 1,3-diol grouping are non-alkoxylated.
Alkoxylated alcohols can be obtained by reacting at least one alcohol with at least one alkylene oxide, such as ethylene oxide, propylene oxide and/or butylene oxide. A suitable alkoxylation degree is for instance 0.5-10, that is 0.5-10 moles of said alkylene oxide on 1 mole of said alcohol. Selectively alkoxylated alcohols are for instance obtained from triols, tetrols and higher alcohols having for instance a 1,3-diol grouping of formula (III) wherein R2 and/or R3 are for instance hydroxyalkyl. The hydroxyl groups of the 1,3-diol grouping of said formula (I) are before alkoxylation protected and subsequent said alkoxylation deprotected. A suitable protection method is for instance acetal formation. Further suitable protection and deprotection methods are disclosed in for instance xe2x80x9cProtective Groups in Organic Synthesisxe2x80x9d chapter 2 xe2x80x9cProtection for the Hydroxyl Group, Including 1,2- and 1,3-diolsxe2x80x9d by Theodora W. Greene and Peter G. M. Wuts, John Wiley and Sons 1991.
The catalyst used in preferred embodiments of the present invention can suitably be exemplified by KOH, K2CO3, NaOH, Na2CO3, LiOH, Li2CO3, KH, NaH, LiH, KNH2, NaNH2, LiNH2, MgCO3, Sr(OH)2, Zn(OH)2, Zn(OR)2 wherein OR is alkoxide having 1 to 4 carbon atoms, elemental Na, elemental Li, 2-N(R)2-pyridine or 4N(R)2-pyridine wherein R is hydrogen or C1-C18 alkyl, trialkylamines, triarylphospine, ZnO, Zn(II)acetate, Zn(O2CR)2 wherein R is C2-C17 hydrocarbyl, Zn(X)2 wherein X is F, Cl, Dr or I, Bu2SnO or Bu2Sn(OR)2 wherein Bu is butyl and OR is alkoxide having 1 to 4 carbon atoms, Ti(OR)4 or Zr(OR)4 wherein OR is alkoxide having 1 to 4 carbon atoms, Ti(X)4 or Zr(X)4 wherein X is F, Cl, Br or I, AlH(R)2 wherein R is C1-C12, AlCl3, FeCl3 or Fe(III)acetylacetonate or is a combination of two or more of said compounds.
The oxetane yielded and recovered from the process of the present invention is in the most preferred embodiments a compound of general formula (IV) 
wherein each R7 and R8 independently is alkyl, alkyloxy, alkyloxyalkyl, aryloxyalkyl, hydroxyalkyl, hydroxyalkyloxy, aryl or hydroxyaryl and wherein each R9 independently is hydrogen or alkyl. Said alkyl preferably is linear or branched alkanyl or alkenyl having 1-24, such as 3-24, 1-12, 4-12 or 2-8, carbon atoms. Substituents R7 and R8 can optionally and where applicable suitably comprise one or more oxetane rings of formula (I). The oxetane is in especially preferred embodiments an oxetane of trimethylolethane, trimethylolpropane, pentaerythritol, ditrimethylolethane, ditrimethylolpropane or dipentaerythritol or is an oxetane of a selectively alkoxylated, such as said ethoxylated and/or propoxylated, trimethylolethane, trimethylolpropane, pentaerythritol, ditrimethylolethane, ditrimethylolpropane or dipentaerythritol. Selectively alkoxylated is interpreted and suitably exemplified as disclosed previously, whereby said oxetane in these embodiments preferably is an oxetane of a 2-alkyl-2-hydroxyalkyloxy-1,3-propanediol, a 2,2-di(hydroxyalkyloxy)-1,3-propanediol or a dimer, trimer or polymer of said 1,3-propanediol Said alkyloxy is as previously disclosed preferably linear or branched having 3-24, such as 4-12, carbon atoms.
The reaction mixture yielded from the reaction, included in the process of the present invention, between carbamide and alcohol may in addition to said oxetane comprise an orthocarbonate of said alcohol as reaction by-product. Conditions and molar ratio in the process of the present invention may be varied to obtain an orthocarbonate of general formula (V) 
wherein each R5 independently is alkyl, alkyloxy, alkyloxyalkyl, aryloxyalkyl, hydroxyalkyl, hydroxyalkyloxy, aryl or hydroxyaryl and wherein each R6 independently is hydrogen or alkyl. Said alkyl is preferably linear or branched alkanyl or alkenyl having 1-24, such as 3-24, 1-12, 4-12 or 2 to 8, carbon atoms. The orthocarbonate may be recovered by methods such as recrystallisation, distillation, extraction, chromatography and the like, and optionally decomposed, such as hydrolysed under acidic conditions, whereby at least said alcohol is yielded, recovered and preferably recirculated for reaction with carbamide in accordance with the process of the present invention. In cases where conditions are chosen to allow formation of considerable amounts of the orthocarbonate this may either be separated from yielded reaction mixture and recovered as a separate product, or may as disclosed above be hydrolysed to original alcohol and used to repeat the process after addition of a proper amount of carbamide.
These and other objects and the attendant advantages will be more fully understood from the following detailed description, taken in conjunction with embodiment Examples 1-9.
Examples 1-6, 11 and 12 refer to syntheses in accordance with embodiments of the present invention, yielding an oxetane and in Examples 1-4, 11 and 12 a spiro-orthocarbonate as by-product.
Example 7 refer to NMR characterisation of the oxetane obtained in Examples 1-6.
Example 8 refer to NMR characterisation of the by-product obtained in Examples 1-4.
Example 9 refer to hydrolytic decomposition of the spiro-orthocarbonate obtained in Example 3.
Example 10 refer to synthesis of an oxetane using the alcohol obtained from the decomposition of the spiro-orthocarbonate of Example 9.